Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function
The NLRP3 inflammasome is primarily known for producing inflammatory cytokines and inducing pyroptosis. Stuart and colleagues identify an additional role for NLRP3 in driving down the pH of phagosomes. Phagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates micr...
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| Veröffentlicht in: | Nature immunology 2013-06, Vol.14 (6), p.543-553 |
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| creator | Sokolovska, Anna Becker, Christine E Ip, W K Eddie Rathinam, Vijay A K Brudner, Matthew Paquette, Nicholas Tanne, Antoine Vanaja, Sivapriya K Moore, Kathryn J Fitzgerald, Katherine A Lacy-Hulbert, Adam Stuart, Lynda M |
| description | The NLRP3 inflammasome is primarily known for producing inflammatory cytokines and inducing pyroptosis. Stuart and colleagues identify an additional role for NLRP3 in driving down the pH of phagosomes.
Phagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates microbial killing, innate immune activation and antigen presentation. An essential step in this process is phagosome acidification, which regulates many functions of these organelles that allow phagosomes to participate in processes that are essential to both innate and adaptive immunity. Here we report that acidification of phagosomes containing Gram-positive bacteria is regulated by the NLRP3 inflammasome and caspase-1. Active caspase-1 accumulates on phagosomes and acts locally to control the pH by modulating buffering by the NADPH oxidase NOX2. These data provide insight into a mechanism by which innate immune signals can modify cellular defenses and establish a new function for the NLRP3 inflammasome and caspase-1 in host defense. |
| doi_str_mv | 10.1038/ni.2595 |
| format | Article |
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Phagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates microbial killing, innate immune activation and antigen presentation. An essential step in this process is phagosome acidification, which regulates many functions of these organelles that allow phagosomes to participate in processes that are essential to both innate and adaptive immunity. Here we report that acidification of phagosomes containing Gram-positive bacteria is regulated by the NLRP3 inflammasome and caspase-1. Active caspase-1 accumulates on phagosomes and acts locally to control the pH by modulating buffering by the NADPH oxidase NOX2. These data provide insight into a mechanism by which innate immune signals can modify cellular defenses and establish a new function for the NLRP3 inflammasome and caspase-1 in host defense.</description><identifier>ISSN: 1529-2908</identifier><identifier>EISSN: 1529-2916</identifier><identifier>DOI: 10.1038/ni.2595</identifier><identifier>PMID: 23644505</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/250/262 ; Acidification ; Animals ; Bacteria ; Biomedicine ; Carrier Proteins - immunology ; Carrier Proteins - metabolism ; Caspase 1 - immunology ; Caspase 1 - metabolism ; Cells, Cultured ; Enzyme Activation - immunology ; Flow Cytometry ; Genetic aspects ; Health aspects ; HEK293 Cells ; Host-Pathogen Interactions - immunology ; Humans ; Hydrogen-Ion Concentration ; Immunoblotting ; Immunology ; Infectious Diseases ; Inflammasomes - immunology ; Inflammasomes - metabolism ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages - microbiology ; Membrane Glycoproteins - immunology ; Membrane Glycoproteins - metabolism ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Microscopy, Confocal ; Microscopy, Electron ; NADPH Oxidase 2 ; NADPH Oxidases - immunology ; NADPH Oxidases - metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein ; Oxidases ; Phagocytosis - immunology ; Phagosomes ; Phagosomes - immunology ; Phagosomes - metabolism ; Phagosomes - microbiology ; Phagosomes - ultrastructure ; Physiological aspects ; Reactive Oxygen Species - immunology ; Reactive Oxygen Species - metabolism ; Staphylococcus aureus - immunology ; Staphylococcus aureus - physiology</subject><ispartof>Nature immunology, 2013-06, Vol.14 (6), p.543-553</ispartof><rights>Springer Nature America, Inc. 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c630t-515d9e07cd4ed325343ba2d0accd3b87da63f794c16d7e96503de4b872fdaf5c3</citedby><cites>FETCH-LOGICAL-c630t-515d9e07cd4ed325343ba2d0accd3b87da63f794c16d7e96503de4b872fdaf5c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ni.2595$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ni.2595$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,777,781,882,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23644505$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sokolovska, Anna</creatorcontrib><creatorcontrib>Becker, Christine E</creatorcontrib><creatorcontrib>Ip, W K Eddie</creatorcontrib><creatorcontrib>Rathinam, Vijay A K</creatorcontrib><creatorcontrib>Brudner, Matthew</creatorcontrib><creatorcontrib>Paquette, Nicholas</creatorcontrib><creatorcontrib>Tanne, Antoine</creatorcontrib><creatorcontrib>Vanaja, Sivapriya K</creatorcontrib><creatorcontrib>Moore, Kathryn J</creatorcontrib><creatorcontrib>Fitzgerald, Katherine A</creatorcontrib><creatorcontrib>Lacy-Hulbert, Adam</creatorcontrib><creatorcontrib>Stuart, Lynda M</creatorcontrib><title>Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function</title><title>Nature immunology</title><addtitle>Nat Immunol</addtitle><addtitle>Nat Immunol</addtitle><description>The NLRP3 inflammasome is primarily known for producing inflammatory cytokines and inducing pyroptosis. Stuart and colleagues identify an additional role for NLRP3 in driving down the pH of phagosomes.
Phagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates microbial killing, innate immune activation and antigen presentation. An essential step in this process is phagosome acidification, which regulates many functions of these organelles that allow phagosomes to participate in processes that are essential to both innate and adaptive immunity. Here we report that acidification of phagosomes containing Gram-positive bacteria is regulated by the NLRP3 inflammasome and caspase-1. Active caspase-1 accumulates on phagosomes and acts locally to control the pH by modulating buffering by the NADPH oxidase NOX2. These data provide insight into a mechanism by which innate immune signals can modify cellular defenses and establish a new function for the NLRP3 inflammasome and caspase-1 in host defense.</description><subject>631/250/262</subject><subject>Acidification</subject><subject>Animals</subject><subject>Bacteria</subject><subject>Biomedicine</subject><subject>Carrier Proteins - immunology</subject><subject>Carrier Proteins - metabolism</subject><subject>Caspase 1 - immunology</subject><subject>Caspase 1 - metabolism</subject><subject>Cells, Cultured</subject><subject>Enzyme Activation - immunology</subject><subject>Flow Cytometry</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>HEK293 Cells</subject><subject>Host-Pathogen Interactions - immunology</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Immunoblotting</subject><subject>Immunology</subject><subject>Infectious Diseases</subject><subject>Inflammasomes - immunology</subject><subject>Inflammasomes - metabolism</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Macrophages - microbiology</subject><subject>Membrane Glycoproteins - immunology</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mice</subject><subject>Mice, 129 Strain</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Confocal</subject><subject>Microscopy, Electron</subject><subject>NADPH Oxidase 2</subject><subject>NADPH Oxidases - immunology</subject><subject>NADPH Oxidases - metabolism</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein</subject><subject>Oxidases</subject><subject>Phagocytosis - immunology</subject><subject>Phagosomes</subject><subject>Phagosomes - immunology</subject><subject>Phagosomes - metabolism</subject><subject>Phagosomes - microbiology</subject><subject>Phagosomes - ultrastructure</subject><subject>Physiological aspects</subject><subject>Reactive Oxygen Species - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sokolovska, Anna</au><au>Becker, Christine E</au><au>Ip, W K Eddie</au><au>Rathinam, Vijay A K</au><au>Brudner, Matthew</au><au>Paquette, Nicholas</au><au>Tanne, Antoine</au><au>Vanaja, Sivapriya K</au><au>Moore, Kathryn J</au><au>Fitzgerald, Katherine A</au><au>Lacy-Hulbert, Adam</au><au>Stuart, Lynda M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function</atitle><jtitle>Nature immunology</jtitle><stitle>Nat Immunol</stitle><addtitle>Nat Immunol</addtitle><date>2013-06-01</date><risdate>2013</risdate><volume>14</volume><issue>6</issue><spage>543</spage><epage>553</epage><pages>543-553</pages><issn>1529-2908</issn><eissn>1529-2916</eissn><abstract>The NLRP3 inflammasome is primarily known for producing inflammatory cytokines and inducing pyroptosis. Stuart and colleagues identify an additional role for NLRP3 in driving down the pH of phagosomes.
Phagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates microbial killing, innate immune activation and antigen presentation. An essential step in this process is phagosome acidification, which regulates many functions of these organelles that allow phagosomes to participate in processes that are essential to both innate and adaptive immunity. Here we report that acidification of phagosomes containing Gram-positive bacteria is regulated by the NLRP3 inflammasome and caspase-1. Active caspase-1 accumulates on phagosomes and acts locally to control the pH by modulating buffering by the NADPH oxidase NOX2. These data provide insight into a mechanism by which innate immune signals can modify cellular defenses and establish a new function for the NLRP3 inflammasome and caspase-1 in host defense.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>23644505</pmid><doi>10.1038/ni.2595</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/250/262 Acidification Animals Bacteria Biomedicine Carrier Proteins - immunology Carrier Proteins - metabolism Caspase 1 - immunology Caspase 1 - metabolism Cells, Cultured Enzyme Activation - immunology Flow Cytometry Genetic aspects Health aspects HEK293 Cells Host-Pathogen Interactions - immunology Humans Hydrogen-Ion Concentration Immunoblotting Immunology Infectious Diseases Inflammasomes - immunology Inflammasomes - metabolism Macrophages - immunology Macrophages - metabolism Macrophages - microbiology Membrane Glycoproteins - immunology Membrane Glycoproteins - metabolism Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Microscopy, Confocal Microscopy, Electron NADPH Oxidase 2 NADPH Oxidases - immunology NADPH Oxidases - metabolism NLR Family, Pyrin Domain-Containing 3 Protein Oxidases Phagocytosis - immunology Phagosomes Phagosomes - immunology Phagosomes - metabolism Phagosomes - microbiology Phagosomes - ultrastructure Physiological aspects Reactive Oxygen Species - immunology Reactive Oxygen Species - metabolism Staphylococcus aureus - immunology Staphylococcus aureus - physiology |
| title | Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function |
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